THERAPEUTICAL EVALUATION OF BIOACTIVE COMPOUNDS OF NIGELLA SATIVA FOR HER2-POSITIVE BREAST CANCER TREATMENT
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Keywords
Nigella sativa, Phytochemicals, Molecular docking, HER2+BC, Treatment
Abstract
This study aims to discover the mechanisms by which phytoactive compounds from Nigella sativa exert anti-breast cancer effects through in-silico analysis, exploring their potential as promising therapeutic candidates against HER2-positive breast cancer treatment in particular. For this purpose, human epidermal growth factor receptor 2 was chosen based on their high protein-protein interaction scores. The protein sequence was retrieved from databases such as NCBI and UniProt. Structural modeling was performed using the SWISS-MODEL platform, Structural validation identified by the SAVES server and TM-align. Ligand preparations involved selecting ligands including 4-terpineol, Nigellidine, Carvacrol, Thymol, and Thymoquinone from the ChEBI database and filtering for specific criteria. Protein-ligand docking analysis was carried out using the PyRx program. ADME analysis performed by SwissADME. The target protein is a protease involved in the regulation of fetal growth and HER2+ breast cancer. Several compounds, such as 4-terpineol, Nigellidine, Carvacrol, Thymol, and Thymoquinone exhibit promising binding potential towards the target protein, with an affinity of -9.8 kcal/mol and rmsd scores of 21.079 and 18.688 angstroms, respectively. The results of this study provide a solid starting point for the development and offer potential therapeutic applications across therapeutics. It provides novel insights into candidates' properties as potential HER2 inhibitors, highlighting molecules like Nigellidine for further preclinical development against aggressive HER2-positive breast cancer treatment driven by this pathway pending more research.
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Asif Bilal
Department of Zoology, University of Okara, Okara Pakistan
Fouzia Tanvir
Department of Zoology, University of Okara, Okara Pakistan
Sibtain Ahmad
Institute of Animal and Dairy Sciences, Faculty of Animal Husbandry, University of Agriculture, Faisalabad, Pakistan
Abdur Rehman Azam
Department of Pathobiology, College of veterinary medicine, University of Illinois at Urbana Champaign, USA
Muhammad Qasim
Department of Zoology, University of Lahore Sargodha Campus, Sargodha Pakistan
Hasnain Zafar
Institute of Zoology, Bahauddin Zakariya university, Multan, Pakistan